Extramural papers of the month
By Nancy Lamontagne
- Triclosan associated with liver damage in mice
- Potential treatment for Parkinson’s targets mitochondrial dysfunction
- Biomonitoring studies should include phosphate flame retardants
- Killifish used to find genes that allow environmental adaptation
Triclosan associated with liver damage in mice
NIEHS grantees report that mice with long-term exposure to the antibacterial agent triclosan experienced fibrosis and acceleration of cancer development in the liver. These findings add to earlier reports that this widely used antimicrobial agent can disrupt hormones and impair muscle contraction.
The researchers exposed mice to triclosan for six months, which equates to about 18 human years. The triclosan-treated mice exhibited cell proliferation, liver fibrosis, and proinflammatory responses that together form the type of environment within which human liver cancer forms. The researchers also chemically induced liver tumors in the mice and found that the mice exposed to triclosan had a large increase in tumor multiplicity, size, and incidence compared to unexposed mice. Findings from the study suggests that triclosan’s negative effects on the liver may result from interference with the constitutive androstane receptor, which plays a role in clearing foreign chemicals from the body.
The authors recommend that because the findings strongly suggest there are adverse health effects in mice with long-term exposure, the relevance of triclosan liver toxicity to humans should be evaluated. They also pointed out that eliminating the use of triclosan in products that are high volume but low benefit, such as hand soaps, would help lessen exposure.
Citation: Yueh MF, Taniguchi K, Chen S, Evans RM, Hammock BD, Karin M, Tukey RH. 2014. The commonly used antimicrobial additive triclosan is a liver tumor promoter. Proc Natl Acad Sci U S A 111(48):17200-17205. (See story.)
Potential treatment for Parkinson’s targets mitochondrial dysfunction
Research supported in part by NIEHS showed that inhibiting a protein required for mitochondrial fission brought positive effects in experimental mouse models of Parkinson’s disease. These findings could lead to a treatment that would target the neuronal mitochondrial dysfunction that is associated with Parkinson’s.
Mitochondria frequently change shape, size, number, and location through the processes of fission and fusion. To determine whether targeting fission and fusion might have a therapeutic effect on Parkinson’s, researchers used mice that model the mitochondrial impairments seen in the disease.
They found that targeting fission, which produces smaller and more motile mitochondria, was beneficial in the animal models studied. Fission requires the recruitment of the GTPase dynamin-related protein-1 (Drp1) from the cytosol to the outer mitochondrial membrane. By blocking Drp1 using gene-therapy or a chemical approach, the researchers reduced both cell death and the deficits in dopamine release, effectively reversing the Parkinson’s disease process.
Citation: Rappold PM, Cui M, Grima JC, Fan RZ, de Mesy-Bentley KL, Chen L, Zhuang X, Bowers WJ, Tieu K. 2014. Drp1 inhibition attenuates neurotoxicity and dopamine release deficits in vivo. Nat Commun 5:5244.
Biomonitoring studies should include phosphate flame retardants
Based on their analysis of phosphate flame retardant (PFR) metabolite levels in people living in California, an NIEHS grantee and colleagues recommend that future biomonitoring studies include the six major metabolites of the most prominent PFRs.
PFR use is increasing as manufacturers seek replacements for the banned pentabromodiphenyl ether mixtures that were previously used as flame retardants. PFRs are detected at higher concentrations than other flame retardants found in house dust, but little is known about how house dust concentrations relate to biological levels. To find out more, the researchers analyzed urine samples from 16 California residents for the six expected major metabolites of the most prominent PFRs and qualitatively screened for 18 other metabolites predicted from in vitro studies. They also collected dust samples and information about home furniture from the participants.
Although this is the first known U.S. study to measure all six major PFR metabolites, the researchers detected the compounds at levels similar to those reported in previous European studies, although few comparisons are available. For many PFR combinations, metabolite levels were correlated, suggesting they commonly co-occur. Two of the metabolite-parent pairs studied showed weakly positive nonsignificant correlations between urine and dust samples. The researchers recommended including certain PFRs in future biomonitoring studies.
Citation: Dodson RE, Van den Eede N, Covaci A, Perovich LJ, Brody JG, Rudel RA. 2014. Urinary biomonitoring of phosphate flame retardants: levels in California adults and recommendations for future studies. Environ Sci Technol 48(23):13625-13633.
Killifish used to find genes that allow environmental adaptation
Research funded in part by NIEHS has identified genes and gene regulation processes that allow killifish to transform the function and structure of its freshwater gills for use in salt water. These findings provide insight into how genes might interact with the environment and evolve toward the development of traits that can more easily respond to environmental changes.
The researchers previously observed that killifish are more vulnerable to arsenic during changes in salinity. Since arsenic prevents killifish from shifting between freshwater and seawater, they reasoned that arsenic could be used to identify which genes orchestrate these changes. The researchers exposed killifish to arsenic while they were acclimating to various levels of salinity and found that the genes orchestrating the killifish response were maintained at precise levels. These results suggest strict regulatory control of these genes may be a general feature of plastic responses in other organisms.
The investigators also found that plasticity-enabling genes seem to be organized in unusually simple networks. Natural selection acts on these networks differently, depending on the degree of plasticity required. Thus, killifish living in stable environments have less precise regulatory control over plasticity-enabling genes than do killifish living in unstable environments.
Citation: Shaw JR, Hampton TH, King BL, Whitehead A, Galvez F, Gross RH, Keith N, Notch E, Jung D, Glaholt SP, Chen CY, Colbourne JK, Stanton BA. 2014. Natural selection canalizes expression variation of environmentally induced plasticity-enabling genes. Mol Biol Evol 31(11):3002-3015.
(Nancy Lamontagne is a science writer with MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)